Long-term Behaviour of 239Pu, 241Am and 233U in Different Bones of One-year-old Rats: Macrodistribution and Macrodosimetry

1984 ◽  
Vol 3 (6) ◽  
pp. 469-483 ◽  
Author(s):  
W. Sontag

1 Female and male rats of the Sprague-Dawley strain, aged about 13 months, were injected intravenously with monomeric 239Pu-(30.7 kBq/kg), 241Am-(54.8 kBq/kg) or 233U-citrate (56.6 kBq/kg) and killed between 7 and 540 days after injection. 2 In both sexes the wet skeletal weight was proportional to body weight; however, the skeletal weight of female rats remained constant, whereas the skeletal weight, and body weight, of male rats increased as a function of age. 3 The initial skeletal deposition decreased in the order 239Pu > 241Am > 233U and for americium and uranium was greater in male rats. The 'half-time' of retention of plutonium and americium was considerably greater than 1 year but the corresponding values for uranium were 140 (females) and 80 (males) days. 4. The relative concentration of the radionuclides in the skeleton varied between 0.2 and 2.0, the variation was greatest for plutonium and lowest for americium and decreased with increasing time after injection. 5 For calculation of the nuclide content of the whole skeleton the most suitable reference bone was found to be the humerus in the case of uranium, and the femur and humerus for plutonium and americium. 6 The cumulative mean skeletal absorbed radiation dose 1 year after injection decreased in the order 239Pu > 241 Am > 233U; for plutonium it was equal for both sexes, whereas for americium and uranium it was 1.5 times higher in male than in females rats. In the individual bones the cumulative dose was greatest in the vertebral column, except the tail, and lowest in the paws.

2000 ◽  
Vol 1 (2) ◽  
pp. 89-100 ◽  
Author(s):  
Masami Shinohara ◽  
Taku Masuyama ◽  
Toshiyuki Shoda ◽  
Tadakazu Takahashi ◽  
Yoshiaki Katsuda ◽  
...  

A new spontaneously diabetic strain of the Sprague-Dawley rat was established in 1997 and named the SDT (Spontaneously Diabetic Torii) rat. In this research, we investigated the characteristics of the disease condition in the SDT rats. The time of onset of glucosuria was different between male and female SDT rats; glucosuria appeared at approximately 20 weeks of age in male rats and at approximately 45 weeks of age in female rats. A cumulative incidence of diabetes of 100% was noted by 40 weeks of age in male rats, while it was only 33.3% even by 65 weeks of age in female rats. The survival rate up to 65 weeks of age was 92.9% in male rats and 97.4% in female rats. Glucose intolerance was observed in male rats from 16 weeks of age. The clinical characteristics of the male SDT rats were (1) hyperglycemia and hypoinsulinemia (from 25 weeks of age); (2) long-term survival without insulin treatment; (3) hypertriglyceridemia (by 35 weeks of age); however, no obesity was noted in any of the male rats. The histopathological characteristics of the male rats with diabetes mellitus (DM) were (1) fibrosis of the pancreatic islets (by 25 weeks of age); (2) cataract (by 40 weeks of age); (3) tractional retinal detachment with fibrous proliferation (by 70 weeks of age) and (4) massive hemorrhaging in the anterior chamber (by 77 weeks of age). These clinical and histopathological characteristics of the disease in SDT rats resemble those of human Type 2 diabetes with insulin hyposecretion. In conclusion, SDT rat is considered to be a potentially useful model for studies of diabetic retinopathy encountered in humans.


2020 ◽  
Vol 10 (5) ◽  
pp. 270 ◽  
Author(s):  
Samuel J. Hogarth ◽  
Elvan Djouma ◽  
Maarten van den Buuse

Alcohol use disorder (AUD) is a detrimental disease that develops through chronic ethanol exposure. Reduced brain-derived neurotrophic factor (BDNF) expression has been associated with AUD and alcohol addiction, however the effects of activation of BDNF signalling in the brain on voluntary alcohol intake reinstatement and relapse are unknown. We therefore trained male and female Sprague Dawley rats in operant chambers to self-administer a 10% ethanol solution. Following baseline acquisition and progressive ratio (PR) analysis, rats were split into drug and vehicle groups during alcohol lever extinction. The animals received two weeks of daily IP injection of either the BDNF receptor, TrkB, agonist, 7,8-dihydroxyflavone (7,8-DHF), or vehicle. During acquisition of alcohol self-administration, males had significantly higher absolute numbers of alcohol-paired lever presses and a higher PR breakpoint. However, after adjusting for body weight, the amount of ethanol was not different between the sexes and the PR breakpoint was higher in females than males. Following extinction, alcohol-primed reinstatement in male rats was not altered by pretreatment with 7,8-DHF when adjusted for body weight. In contrast, in female rats, the weight-adjusted potential amount of ethanol, but not absolute numbers of active lever presses, was significantly enhanced by 7,8-DHF treatment during reinstatement. Analysis of spontaneous locomotor activity in automated photocell cages suggested that the effect of 7,8-DHF was not associated with hyperactivity. These results suggest that stimulation of the TrkB receptor may contribute to reward craving and relapse in AUD, particularly in females.


2016 ◽  
Vol 116 (1) ◽  
pp. 59-69 ◽  
Author(s):  
Majdi Masarwi ◽  
Yankel Gabet ◽  
Oleg Dolkart ◽  
Tamar Brosh ◽  
Raanan Shamir ◽  
...  

AbstractThe aim of the present study was to determine whether the type of protein ingested influences the efficiency of catch-up (CU) growth and bone quality in fast-growing male rats. Young male Sprague–Dawley rats were either fed ad libitum (controls) or subjected to 36 d of 40 % food restriction followed by 24 or 40 d of re-feeding with either standard rat chow or iso-energetic, iso-protein diets containing milk proteins – casein or whey. In terms of body weight, CU growth was incomplete in all study groups. Despite their similar food consumption, casein-re-fed rats had a significantly higher body weight and longer humerus than whey-re-fed rats in the long term. The height of the epiphyseal growth plate (EGP) in both casein and whey groups was greater than that of rats re-fed normal chow. Microcomputed tomography yielded significant differences in bone microstructure between the casein and whey groups, with the casein-re-fed animals having greater cortical thickness in both the short and long term in addition to a higher trabecular bone fraction in the short term, although this difference disappeared in the long term. Mechanical testing confirmed the greater bone strength in rats re-fed casein. Bone quality during CU growth significantly depends on the type of protein ingested. The higher EGP in the casein- and whey-re-fed rats suggests a better growth potential with milk-based diets. These results suggest that whey may lead to slower bone growth with reduced weight gain and, as such, may serve to circumvent long-term complications of CU growth.


2005 ◽  
Vol 93 (5) ◽  
pp. 613-618 ◽  
Author(s):  
Takahiro Kawasaki ◽  
Akiko Kashiwabara ◽  
Tadashi Sakai ◽  
Kanji Igarashi ◽  
Nobuyuki Ogata ◽  
...  

The current epidemic of diabetes likely reflects marked changes in environmental factors, although genetic susceptibility plays a powerful role in the occurrence of diabetes in certain populations. We investigated whether long-term sucrose-drinking causes hyperglycaemia in male Wistar-Imamichi littermates (n 32), which are not genetically susceptible to diabetes or obesity. Each litter was divided equivalently into two groups, the sucrose group and the control group. The sucrose group received 300 g/l sucrose water and the control group received regular water until 42 weeks of age. Rats were weighed every 1 or 2 weeks. Oral glucose tolerance tests were performed at 28 and 36 weeks of age. Plasma glucose and insulin concentrations were measured. Body weights were significantly greater in the sucrose group than in the control group in 18-week-old rats (P<0·05), and the difference between the two groups reached 163 g by the end of the study (P<0·01). The 120 min post-load plasma glucose concentration in the sucrose group was 11·4 (sd 2·8) mmol/l in 28-week-old rats and 12·7 (sd 2·2) mmol/l in 36-week-old rats, while that of the control group remained approximately 7·3–7·7 mmol/l. In the sucrose group, the plasma insulin peak occurred 30 min post-load at 28 weeks of age; but the peak disappeared and hyperinsulinaemia was prolonged at 36 weeks of age. In conclusion, long-term sucrose-drinking causes increased body weight and glucose intolerance in normal male rats.


2021 ◽  
Vol 22 (16) ◽  
pp. 8935
Author(s):  
In-Song Lee ◽  
Dae-Won Kim ◽  
Ji-Hyeon Oh ◽  
Suk Keun Lee ◽  
Je-Yong Choi ◽  
...  

4-Hexylresorcinol (4HR) has been used as a food additive, however, it has been recently demonstrated as a Class I histone deacetylase inhibitor (HDACi). Unlike other HDACi, 4HR can be taken through foods. Unfortunately, some HDACi have an influence on craniofacial growth, therefore, the purpose of this study was to evaluate the effects of 4HR on craniofacial growth. Saos-2 cells (osteoblast-like cells) were used for the evaluation of HDACi and its associated activities after 4HR administration. For the evaluation of craniofacial growth, 12.8 mg/kg of 4HR was administered weekly to 4 week old rats (male: 10, female: 10) for 12 weeks. Ten rats were used for untreated control (males: 5, females: 5). Body weight was recorded every week. Serum and head samples were collected at 12 weeks after initial administration. Craniofacial growth was evaluated by micro-computerized tomography. Serum was used for ELISA (testosterone and estrogen) and immunoprecipitation high-performance liquid chromatography (IP-HPLC). The administration of 4HR (1–100 μM) showed significant HDACi activity (p < 0.05). Body weight was significantly different in male rats (p < 0.05), and mandibular size was significantly smaller in 4HR-treated male rats with reduced testosterone levels. However, the mandibular size was significantly higher in 4HR treated female rats with increased growth hormone levels. In conclusion, 4HR had HDACi activity in Saos-2 cells. The administration of 4HR on growing rats showed different responses in body weight and mandibular size between sexes.


2020 ◽  
Vol 150 (7) ◽  
pp. 1713-1721
Author(s):  
Hai-Ping Wu ◽  
Yu-Shun Lin ◽  
Chi-Fen Chang ◽  
Shui-Yuan Lu ◽  
Pei-Min Chao

ABSTRACT Background Dietary frying oil may have endocrine-disrupting effects, as a feminization effect was observed in cohorts of C57BL/6J male mice fetuses from dams consuming oxidized frying oil (OFO) during pregnancy. Objective The aim of present study was to test the hypothesis that OFO is an anti-androgen. Methods In experiment 1, male progeny of Sprague Dawley female rats fed fresh oil or an OFO diet (10 g fat/100 g, from fresh or 24-h–fried soybean oil; [control diet (C) and OFO groups, respectively] from midgestation through lactation were studied. Pups were weaned at 3 wk of age and then consumed their mothers’ diet until 9 wk of age. In addition, a group of dams and pups that consumed a high-fat diet (HF; 10 g fried and 20 g fresh soybean oil/100 g) was included to counteract body-weight loss associated with OFO ingestion. Indices of male reproductive development and testosterone homeostasis were measured. In experiment 2, male rats were allocated to C and OFO groups (treated as above) and indices of male fertility compared at 9–10 wk of age. Results In experiment 1, final body weights of the HF group were lower (17%) than the C group but higher (14%) than the OFO group (P &lt; 0.0001 for each). In addition to abnormalities in seminiferous tubules, HF and OFO groups did not differ from one another, but, compared with the C group, had delayed preputial separation (4.9 d) and reductions in serum testosterone concentrations (17–74%), anogenital distance (8–20%), weights of androgen-dependent tissues (8–30%), testicular testosterone and cholesterol concentrations (30–40%), and mRNA levels of genes involved in steroidogenesis and cholesterol homeostasis (30–70%). In experiment 2, OFO-exposed males had 20% lower sperm motility (P &lt; 0.05); however, when mated to normal females, pregnancy rates and litter sizes did not differ between OFO and C groups. Conclusions The anti-androgenic effect of OFO in Sprague Dawley rats was attributed to decreased testicular concentrations of cholesterol (testosterone precursor) and not body-weight loss.


2014 ◽  
Vol 33 (5) ◽  
pp. 393-402 ◽  
Author(s):  
Richard A. Angerhofer ◽  
Mark W. Michie ◽  
Glenn J. Leach ◽  
Mark S. Johnson ◽  
Gunda Reddy

Thiodiglycol (TDG) is the main product of sulfur mustard hydrolysis and is an environmental contaminant. Subacute and subchronic oral toxicity studies with TDG were conducted in Sprague-Dawley rats. Neat TDG was administered by gavage at doses of 157, 313, 625, 1250, 2500, 5000, and 9999 mg/kg/d, 5 days per week, for 14 days. In the 14-day study, decreased body weight and food consumption were observed at 5000 mg/kg/d. In the 90-day study, rats received neat TDG at doses of 50, 500, or 5000 mg/kg/d for 5 days per week. A fourth group served as a sham control. Individual body weight and food consumption were measured weekly. At termination of the experiment, urine, blood, and tissue samples were collected. Rats displayed significant decreased body weight with no effect on food consumption following administration of TDG at 5000 mg/kg/d. Both male and female rats showed significant increased kidney weights at 5000 mg/kg/d. The organ to body weight ratios increased significantly for liver, kidneys, testes, and brain in males and adrenals in females for 5000 mg/kg/d. At all doses of TDG, hematological and clinical parameters and tissue histopathology remained unaltered. The no observed adverse effect level (NOAEL) for oral subchronic toxicity was 500 mg/kg/d. Benchmark dose (BMD) was derived from the decreased gain in body weight that was seen in male rats. A BMD based on a 10% decrease in body weight was 1704 mg/kg/d, and the lower confidence limit on the dose BMD, the BMDL, was 372 mg/kg/d.


Author(s):  
Redzuan Nul Hakim Abdul Razak ◽  
Suzanah Abdul Rahman ◽  
Asmah Hanim Hamdan ◽  
Roszaman Ramli ◽  
Muhammad Lokman Md Isa ◽  
...  

Aquilaria malaccensis or commonly known as ‘gaharu’ is a species of Aquilaria genus and belongs to the Thymelaeaceae family. It is widely distributed in Malaysia, Indonesia, and the Borneo Islands. Traditionally, its leaves were used to relieve bruises and studies have shown that they function as an antioxidant, aphrodisiac, and tranquilizer. Despite its proven beneficial medicinal properties, information regarding its toxicity is limited. Therefore, we performed a safety evaluation on the aqueous A. malaccensis leaves extract (AMAE) in Sprague Dawley rats. The assessment of acute toxicity based on the Organization for Economic Cooperation and Development (OECD) Guideline 420 revealed that AMAE did not influence mortality, clinical appearance, body weight gain, or necropsy findings at a dose of 2000 mg/kg body weight. In the sub-acute toxicity, all doses did not significantly modify the body weight and food and water intake. In male rats treated with 2000 mg/kg, there was a significant reduction in the relative weight of liver. Not only that, an increase in alkaline phosphatase and alanine transaminase was also observed in different groups among the female rats. A significant decrease in the creatinine level was also seen among male rats administered with different doses of AMAE. In both sexes, histopathological analysis had shown abnormalities in the liver and kidney of rats treated at the dose of 2000 mg/kg. In conclusion, the 50% lethal dose (LD50) of AMAE was estimated to be greater than 2000 mg/kg. In sub-acute duration, the findings suggested that AMAE administered orally is slightly toxic at higher doses (2000 mg/kg) and could provoke functional and structural changes in the kidney and liver of rats. Thus, the extract should be used with caution.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yi Zhang ◽  
Jian Li ◽  
Zhizhen Wu ◽  
Erwei Liu ◽  
Pingping Shi ◽  
...  

The acute toxicity of mango leaves extract (MLE) at the maximal dose (18.4 g/kg) was studied in ICR mice and no abnormalities were detected during the experiment. The long-term studies at various doses of MLE (100 mg/kg, 300 mg/kg, and 900 mg/kg) in SD rats for 3 consecutive months revealed that, compared with the control group, rats in MLE treated groups showed slight body weight increase and higher fat weight; the serum TG and CHOL levels and the epididymis weight of male rats were a little higher; the serum K+level of female rats was on the low side but the weights of liver, kidney, and adrenal gland were on the high side. In addition to this, no other obvious abnormalities were detected.


1979 ◽  
Vol 16 (5) ◽  
pp. 574-582 ◽  
Author(s):  
J. J. Berman ◽  
J. M. Rice

A single intraperitoneal dose of methyl(acetoxymethyl)nitrosamine (13 mg/kg body weight) given to 78 5-week-old male rats induced 25 mesotheliomas; two mesotheliomas were found in 67 control rats. All mesotheliomas arose from the peritesticular mesothelium and had a typical microscopic appearance of branching papillary fronds with a collagenous core covered by one or many layers of plump tumor cells. Cytoplasm of tumor cells contained material that reacted positively to a colloidal iron stain and was labile to hyaluronidase. In addition to frank mesotheliomas, 16 lesions, which we called atypical mesothelial proliferations. were found. These consisted of a single focus of plump mesothelial cells overlying an area of thick stroma. Often these foci included short, non-branched papillary projections above the surface of adjacent normal mesothelium. Twelve of the 16 lesions occurred in methyl(acetoxymethyl)nitrosamine-treated rats.


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